title: Epigenetic regulation in myelodysplastic syndromes: implications for therapy.
abstract: BACKGROUND
  Myelodysplastic syndromes (MDS), characterized by ineffective hematopoiesis and dysplasia in one or more lineages, produce life-threatening cytopenias and progress to acute myeloid leukemia (AML). Growing evidence suggests that targeting epigenetic mechanisms improves MDS/AML pathophysiology.
  
  
  METHODS
  This review provides an understanding of studies investigating novel agents published up to January 2011 aimed at normalizing and monitoring the epigenetic profile of the MDS cancer cell. The authors discuss how non-intensive epigenetic therapy can 're-programme' gene expression patterns of abnormal hematopoiesis in MDS. Recently FDA-approved DNA-methyltransferase inhibitors, 5-azacytidine and 5-aza-2'-deoxycytidine or decitabine, represent frontline nonablative treatments, while combinations with histone deacetylase inhibitors show promising synergism in preclinical and Phase I/II trials in tumor suppressor gene re-expression and overall survival. Additional epigenetic mechanisms including non-encoding transcripts with inhibitory posttranscriptional regulatory functions, such as microRNAs, though not fully understood, present novel molecular and clinical implications in these disorders.
  
  
  CONCLUSIONS
  Alongside current single-agent epigenetic regimens, combination therapies represent potentially effective options for intermediate-2 and high-risk MDS. Methylation profiles and gene mutation predictors provide promising areas of development for monitoring MDS disease progression and outcome, while targeting microRNA dysregulation represents an important therapeutic goal.
authors.affiliation: Unità Operativa Complessa di Ematologia, Dipartimento Oncoematologico, Azienda Ospedaliera di Cosenza, Viale della Repubblica, Cosenza, Italy. fortunato_morabito@tin.it.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Vigna
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Antonio
authors.initials: A
authors.lastname: Madeo
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bossio
authors.forename: Carla
authors.initials: C
authors.lastname: Mazzone
authors.forename: Eugenio
authors.initials: E
authors.lastname: Lucia
authors.forename: Lucio
authors.initials: L
authors.lastname: Morabito
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gigliotti
authors.forename: Laura De
authors.initials: LD
authors.lastname: Stefano
authors.forename: Nadia
authors.initials: N
authors.lastname: Caruso
authors.forename: Pasquale
authors.initials: P
authors.lastname: Servillo
authors.forename: Stefania
authors.initials: S
authors.lastname: Franzese
authors.forename: Filippo
authors.initials: F
authors.lastname: Fimognari
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bisconte
authors.forename: Carlo
authors.initials: C
authors.lastname: Gentile
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D015507:Drugs, Investigational; D056572:Histone Deacetylase Inhibitors